Biol. Pharm. Bull. 29(5) 991—996 (2006)

named as an aquaporin (AQP) in the membrane of erythrocytes in 1991. Thirteen molecular species of AQPs, AQP0—12, have been identified to date. These AQPs were classified into two groups, AQP0, 1, 2, 4, 5, 6, and 8 and AQP3, 7, 9, 10, 11, and 12, the former group selectively permeabilizing water only and the latter, named as aquaglyceroporins, permeabilizing not only water, but also water-soluble low-molecular weight molecules such as glycerol and urea. Although AQPs are widely distributed in almost all human tissues, they show specific tissue localization. AQP1, 3, 4, 7, 8, 10, and 11 were reported to be expressed in the gastrointestinal tract and seem to play a role in absorption of water. However, it is still unclear what substances other than water are permeabilized by these AQPs in these sites. AQP3 has been observed expressed in human ileum, colon, jejunum, liver, and pancreas and highly expressed on basal membrane of epithelial cells in ileum and colon. From observations in AQP3-deficient mice, AQP3 was speculated related to renal failure caused by nephrogenic diabetes insipidus and hydronephrosis, absorption of glycerol from decreases of glycerol levels in serum, skin hydration from promotion of dry skin, and occurrence of diarrhea and constipation. Although lethal dysfunctions caused by deficiency of AQP3 in mice have not been reported so far, AQP3 seems to be required to maintain healthy living. Itoh et al. found that AQP3 expression was increased by treatment with vasoactive intestinal polypeptide (VIP) in human colonic epithelial cells and suggested that increased expression of AQP3 by VIP caused exacerbation of diarrhea because VIP was closely linked to diarrhea onset through controlling gastrointestinal peristaltic motion and secretion of water and electrolytes. The physiological roles related to permeation of low-molecular weight molecules by AQP3 are still unclear in the gastrointestinal tract although the roles on water permeation were studied in depth as described above. mRNA expression of AQP7, a closely related species to AQP3 and classified as an aquaglyceroporin, was reported regulated by insulin in adipose cells. Although the action mechanisms of insulin have been well studied, it has rarely been reported that AQPs are involved in the process of the insulin reaction. The finding of suppression of AQP7 expression by insulin suggests the possibility that insulin controls release of glycerol from adipose cells through AQP7. AQP7 probably contributes to decrease of blood glucose level. Since glycerol is involved in digested nutrients and AQP3 is able to permeabilize glycerol, as dose AQP7, it seems appropriate to consider that AQP3 is responsible for absorption of glycerol in digestive organs. Therefore we first examined whether AQP3 expression was affected by insulin and found that mRNA expression of AQP3 was decreased by treatment with insulin. Herein, we investigate how hormones including insulin and antidiabetic agents used for controlling blood glucose level affect AQP3 expression and the signal transduction pathway from insulin to gene expression of AQP3.